Ara h 2
Summary
Ara h 2 is considered to be one of the major peanut allergens. Ara h 2 is a conglutin seed storage protein and member of the 2S albumin family, which is capable of withstanding the harsh conditions of the gastrointestinal tract. It is estimated that 97% of peanut allergy patients are sensitized to at least one of the allergens Ara h 1, 2 and 3. Individuals who are sensitized to Ara h 2 are at an increased risk for more severe symptoms and anaphylactic reactions, with Ara h 2 being one of most potent, and frequently recognized peanut allergens. Polysensitization to Ara 1, 2 and 3 can help to predict the severity of reaction at challenge. Roasting peanuts at high temperatures increases the allergenicity of Ara h 2. Studies have reported that specific IgE to Ara h 2 can be important in diagnosing peanut allergy in combination with Ara h 1 and 3, or with Ara h 6. Specific IgE to Ara h 2 has been a proposed biomarker to help predict the severity of peanut allergic reactions, although studies have demonstrated conflicting results. However, the authors of a recent meta-analysis suggested that specific IgE to Ara h 2 can reduce the number of oral food challenges in unclear cases and has high diagnostic accuracy for peanut allergy in children across geographic locations. Peanut and tree nuts show cross reactivity in peanut-allergic patients because Ara h 2 shares IgE-binding epitopes with almond and Brazil nut allergens.
Epidemiology
Worldwide distribution
Studies have typically reported peanut allergy prevalence rates between 1–2% in Western nations. Peanut allergy appears to be less common in Asia and other global areas, although epidemiological studies in non-Western regions have been sparse. Peanut allergy usually begins in childhood and persists throughout the affected individual’s lifetime however, approximately 20% of young children develop tolerance.
Typically, the frequency of Ara h 2 sensitization is higher compared to other peanut allergen components. For example, Ara h 2 had the highest frequency of specific IgE binding (85%) in 40 peanut-allergic patients compared to the other peanut allergen components Ara h 1, 3, 5, 6 and 7. The prevalence of Ara h 2 sensitization from a larger study using 12,155 serum samples in the USA was estimated to be 62%, similarly this was higher than the other allergen components. In contrast, a study involving 30 peanut-allergic individuals found that 83% (25/30) of patients with a positive skin prick test (SPT) were sensitized to Ara h 2, with the prevalence of Ara h 6 sensitization being slightly higher at 87% (26/30).
Ara h 2 is considered to be one of the major peanut allergens. It is estimated that 97% of peanut allergy patients are sensitized to at least one of the allergens Ara h 1, 2 and 3. In addition, a UK study found that 84% (42/50) were sensitized to Ara h 2 and 6, with 74% (31/42) having higher levels of Ara h 2-specific IgE than Ara h 6-specific IgE. This is in agreement with an earlier study which concluded that Ara h 2 and 6 were the most frequently recognized major peanut allergens in children. A review by van der Valk et al. (2016) summarized studies assessing the prevalence of cosensitization with Ara h 2 and 6 which ranged from 0 to 90% (e.g. 0, 45, 59, 71, 73, 74, 80, 90%).
Clinical Relevance
Typical clinical symptoms of peanut allergy range from angioedema, urticaria, nausea, abdominal pain, vomiting, wheezing, and breathlessness which usually occur soon after peanut ingestion. Since Ara h 2 is a storage protein, individuals who are sensitized to this component are at an increased risk for more severe symptoms and anaphylactic reactions. Ara h 2 and Ara h 6 are considered to be the most potent peanut allergens. Sensitization to peanut storage proteins, Ara h 1, 2 and 3 was associated with increased quantities of airway and systemic inflammation markers compared to patients who were not sensitized to these peanut allergen components in a population of asthma sufferers. Food hypersensitivity symptoms were also more regularly reported by those sensitized to Ara h 1, 2 and 3 than by any other participants in the study.
In 2010, a study reported that Ara h 2 could be a useful tool to help predict peanut allergy. Another study found specific IgE was positively correlated with clinical severity and Ara h 2 in adult patients (r = 0.63, P = 0.002) but this trend was not observed in children. Kukkonen et al. (2015) found that all of the severely allergic patients were sensitized to Ara h 2 or 6 and this was not associated with age (participant age ranged from 6 to 18 years old). In addition, a study found that sensitization to rAra h 2 and rAra h 1 and/or rAra h 3 appeared to be predictive of more severe reactions. Similarly, the results of a recent study in Australia found that polysensitization to Ara 1, 2 and 3 can help to predict the severity of reaction at challenge.
Cross-reactive Molecules
Similarities in physicochemical properties to known IgE epitopes of 2S albumins could account for clinically observed cross-sensitivity between peanuts and tree nuts.
Diagnostics
Disease Severity
While specific IgE to Ara h 2 has been a proposed biomarker to help predict the severity of peanut allergic reactions, studies have demonstrated conflicting results. However, the authors of a recent meta-analysis publication suggested that specific IgE to Ara h 2 can reduce the number of oral food challenges in unclear cases and has high diagnostic accuracy for peanut allergy in children across geographic locations. Results from a cross-sectional study involving 222 Australian children reported that using a combination of Ara h 1, 2 and 3 for peanut component testing could be helpful to identify patients with peanut allergy. An earlier study found that using the combination of Ara h 1, 2, and 3 resulted in a higher specificity (94%) when diagnosing peanut allergy in Japanese children in comparison to using IgE to Ara h 2 alone resulting in a sensitivity and specificity of 88% and 84%, respectively. However, the sensitivity of using the combination of Ara h 1, 2, and 3 was 31%. A study found that cosensitization to rAra h 2 and rAra h 1 and/or rAra h 3 was predictive of more severe reactions in peanut allergy.
Hemmings et al. (2020) found that Ara h 2 and 6 specific IgE provided the greatest accuracy to diagnose peanut allergy, which is in agreement with results from an earlier double-blind placebo-controlled study. However, variation has been shown in the IgE cross-reactivity between Ara h 2 and 6 and therefore using a mixture of these two 2S albumins may improve diagnostic performance when trying to determine the severity of allergic symptoms.
Cross-Reactivity
Peanut and tree nuts show cross-reactivity in 25 to 50% of peanut-allergic patients because Ara h 2 shares IgE-binding epitopes with almond and Brazil nut allergens. However, despite 2S seed albumin allergens sharing structural similarities, Ara h 2, showed no structural homology with the corresponding regions of Walnut Jug r 1, Pecan Car i 1 or Brazil nut Ber e 1. Although there is a theory of cross-reactivity being dependent on allergens sharing a similar sequence and/or structure, there are experimental data highlighting a lack of relationship between the percentage of shared identity and the ability to bind IgE.
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